SodiUm SeleniTe Adminstration IN Cardiac Surgery (SUSTAIN CSX®-Trial).

Heart Disease Clinical Trial

— SUSTAINCSX  

Official title:

SodiUm SeleniTe Adminstration IN Cardiac Surgery (SUSTAIN CSX®-Trial). A Multicentre Randomized Controlled Trial of High Dose Sodium-selenite Administration in High Risk Cardiac Surgical Patients

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02002247
• Other study ID #: SUSTAIN CSX
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: January 2015
• Est. completion date: July 2021

Study information

• Verified date: May 2021
• Source: Clinical Evaluation Research Unit at Kingston General Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The aim of the investigators' research program is to investigate the effects of perioperative high dose selenium supplementation in high-risk cardiac surgical patients undergoing complicated open heart surgery. The investigators hypothesize that the therapeutic strategy tested in this randomized trial may contribute to a fewer complications, less organ injury and fewer deaths. Before the investigators conducted the large definitive trial, they conducted a pilot study to assess the feasibility of the protocol, and are rolling the pilot patients into the definitive trial.

Description:

Over a million patients undergo open heart surgery annually and this number is likely to accelerate as the population ages and the prevalence of diabetes and cardiovascular disease continue to increase. Unfortunately, death, organ failure, and other serious complications are all too frequent following open heart surgery, especially in some high-risk patient populations. Selenium is a trace element that is important for many of the body's regulatory and metabolic functions especially during times of stress. International members of the study team have shown in a non-randomized study that high dose selenium supplementation was associated with improved clinical outcomes compared to a historical control group. The next step in this program of research is to conduct a randomized trial. The aim of this research program is to investigate the effects of perioperative high dose selenium supplementation in high-risk cardiac surgical patients undergoing complicated open heart surgery. The investigators hypothesize that the therapeutic strategy tested in this randomized trial may contribute to fewer complications, less organ injury and fewer deaths. The investigators propose to conduct a randomized, placebo-controlled, double-blind, multicentre definitive trial of 1400 patients across 20 sites in Germany and Canada, which will include the pilot study patients. An industry partner (Biosyn) will provide the product and some additional support for the European sites. Patients will be randomized to receive either a daily perioperative high-dose selenium or placebo until postoperative day 10 (maximum) or upon earlier discharge from ICU. If the hypothesis is proven true, and this simple, inexpensive nutrient reduces complications and improves recovery of patients undergoing cardiac surgery, there is the potential to dramatically change clinical practice and improve health outcomes.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 1400
• Est. completion date: July 2021
• Est. primary completion date: February 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Adult patients (>/=18 years of age)
• Scheduled to undergo elective or urgent cardiac surgery with the use of cardiopulmonary bypass (CPB) and cardioplegic arrest that exhibit a high perioperative

risk profile as defined by the presence of one or more of the following:

• a) Planned valve surgery combined with CABG or multiple valve replacement/repair surgeries or combined cardiac surgical procedures involving the thoracic aorta; OR
• b) Any cardiac surgery with a high perioperative risk profile, defined as a predicted operative mortality of = 5% (EuroSCORE II). Exclusion Criteria:

We will exclude patients who meet any of the following criteria:

• Isolated procedures (CABG only or valve)
• Known hypersensitivity to sodium-selenite or to any of the constituents of the solution.
• Renal failure requiring dialysis at the point of screening.
• Chronic liver disease as evidenced by a pre-operative total bilirubin >2 mg/dl or 34 umol/L.
• Disabling neuropsychiatric disorders (severe dementia, severe Alzheimer's disease, advanced Parkinson's disease).
• Pregnancy or lactation period.
• Simultaneous participation in another clinical trial of an experimental therapy (co-enrolment acceptable in observational studies or randomized trials of existing therapies if permitted by both steering committees and local ethics boards).
• Patients undergoing heart transplantation or preoperative planned LVAD insertion or complex congenital heart surgery.
• Alternate contacts of investigators (required by German Regulatory Authorities).

Related Conditions & MeSH terms

• Heart Disease
• Heart Diseases

Intervention

Drug:
• sodium selenite
All subjects will receive an IV bolus of 2000µg selenium within 30min after induction of anesthesia via the central venous catheter. After termination of surgery, immediately after admission to the ICU, all patients will receive a second bolus of 2000µg selenium. Then on every further morning during ICU-stay, patients will receive an IV bolus of 1000µg selenium via central or peripheral venous access until death, discharge from ICU to the ward, or for a maximum of 10 days.
• Placebo
All patients will receive an IV bolus of normal saline (equals to 40ml prepared solution) within 30min after induction of anesthesia via the central venous catheter. After termination of surgery, immediately after admission to the ICU, all patients will receive a second bolus of normal saline accordingly. Then on every further morning during ICU-stay, patients will receive an IV bolus of normal saline via central or peripheral venous access until death, discharge from ICU to the ward (treatment may continue in a step down or intermediate care unit), or for a maximum of 10 days.

Locations

Country	Name	City	State
Canada	Hamilton General Hospital	Hamilton	Ontario
Canada	London Health Sciences Centre	London	Ontario
Canada	Institut de cardiologie de Montreal	Montreal	Quebec
Canada	McGill University Health Centre	Montreal	Quebec
Canada	Sacre Coeur	Montreal	Quebec
Canada	Sir Mortimer B. Davis Jewish General Hospital	Montreal	Quebec
Canada	University of Ottawa Heart Institute	Ottawa	Ontario
Canada	IUCPQ	Quebec City	Quebec
Canada	Centre de recherche CIUSSS de l'Estrie CHUS	Sherbrooke	Quebec
Canada	St. Michael's Hospital	Toronto	Ontario
Canada	Sunnybrook Health Sciences Centre	Toronto	Ontario
Canada	Toronto General Hospital	Toronto	Ontario
Germany	RWTH Aachen University Hospital	Aachen
Germany	Klinik und Poliklinik für Anästhesiologie und Operative Intensivmedizin Universitätsklinikum Bonn	Bonn
Germany	Universitätsklinikum Frankfurt	Frankfurt
Germany	Klinik für Her- und Gefäßchirurgie Universitäts-Herzzentrum Freiburg	Freiburg
Germany	Klinik für Herz-, Kinderherz- und Gefäßchirurgie UKGM Giessen	Gießen
Germany	University Medical Center Schleswig-Holstein	Kiel
Germany	Klinik und Poliklinik für Herz- und Thoraxchirurgie Uniklinik Köln	Koln
Germany	Klinik für Anästhesiologie Universitätsmedizin Mainz	Mainz
Germany	Klinik für Anästhesiologie Klinikum der Universität München	München
Germany	Klinik für Anästhesiologie, operative Intensivmedizin und Schmerztherapie Universitätsmedizin Münster, Zentralklinikum	Münster
Germany	Klinikum Oldenburg gGmbH Universitätsklinik für Anästhesiologie / Intensivmedizin / Notfallmedizin / Schmerztherapie	Oldenburg

Sponsors (4)

Lead Sponsor	Collaborator
Daren K. Heyland	biosyn Arzneimittel GmbH, Queen's University, RWTH Aachen University

Countries where clinical trial is conducted

Canada,  Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Laboratory outcomes	To be assessed up to post-operative day (POD) 10 in patients who consent to this optional blood work.; To assess the potential effects of supplementation on selenium levels, safety parameters and other mechanistic markers. Whole blood levels of selenium, selenoprotein P (Sel-P), antibodies against oxidized LDL, markers of inflammation (interleukin[IL]-6, IL-10, TNF alpha) and activity of glutathione-peroxidase (GPx) will be assessed to determine the efficacy of selenium supplementation in these patients.	POD 10
Primary	PODS free days + alive	Evaluate the PODS free days + alive as the primary outcome for the large-scale Phase III trial. We define PODS as the need for life-sustaining therapies (mechanical ventilation, vasopressor therapy, mechanical circulatory support, continuous renal replacement therapy, or intermittent hemodialysis).	30 Day
Secondary	30-Day Mortality	Mortality 30 days post-randomization.	30 Day
Secondary	Hospital Acquired Infections	To be evaluated up to 6 months post-randomization.	30 day
Secondary	Perioperative hemodynamic profile	This includes: mean arterial blood pressure, cardiac power index, systemic vascular resistance, etc... To be assessed up to 6-months post-randomization.	6 months
Secondary	Cardiovascular Complications	This includes: arrhythmias, cardiac arrest, infarction. To be assessed up to 6-months.	6-months
Secondary	Duration of Mechanical Ventilation	To be assessed up to 6-months.	6-months
Secondary	Incidence of post-operative delirium	Assessed by CAM-ICU score. To be assessed up to 6-months.	6-months
Secondary	ICU Length of stay	To be assessed up to 6 months post-randomization.	6-months
Secondary	Hospital Re-admission Rates	To be assessed up to 6-months post-randomization.	6-months
Secondary	Hospital Length of stay	To be assessed up to 6 months post-randomization.	6-months
Secondary	6-Month Survival	To be assessed at 6 months post-randomization.	6-months
Secondary	Quality of Life	Health related quality of life to be assessed up to 6-months post-randomization.	6-months
Secondary	Return to work	Assessed using a questionnaire to determine the patient's ability to return to their pre-operative working capabilities. To be assessed up to 6 months post-randomization.	6-months
Secondary	6-minute walking test	6-minute walking distance	up to 3 months